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Title: Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease
Author: Sánchez-Danés, Adriana
Richaud-Patin, Yvonne
Carballo Carbajal, Iria
Jiménez-Delgado, Senda
Caig, Carles
Mora, Sergio
Di Guglielmo, Claudia
Ezquerra, Mario
Patel, Bindiben
Giralt Torroella, Albert
Canals i Coll, Josep M.
Memo, Maurizio
Alberch i Vié, Jordi
López-Barneo, José
Vila Farré, Miquel
Cuervo, Ana Maria
Tolosa, Eduardo
Consiglio, Antonella
Raya Chamorro, Ángel
Keywords: Dopamina
Malaltia de Parkinson
Cèl·lules mare
Parkinson's disease
Stem cells
Issue Date: May-2012
Publisher: EMBO Press
Abstract: Induced pluripotent stem cells (iPSC) offer an unprecedented opportunity to model human disease in relevant cell types, but it is unclear whether they could successfully model age-related diseases such as Parkinson's disease (PD). Here, we generated iPSC lines from seven patients with idiopathic PD (ID-PD), four patients with familial PD associated to the G2019S mutation in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene (LRRK2-PD) and four age- and sex-matched healthy individuals (Ctrl). Over long-time culture, dopaminergic neurons (DAn) differentiated from either ID-PD- or LRRK2-PD-iPSC showed morphological alterations, including reduced numbers of neurites and neurite arborization, as well as accumulation of autophagic vacuoles, which were not evident in DAn differentiated from Ctrl-iPSC. Further induction of autophagy and/or inhibition of lysosomal proteolysis greatly exacerbated the DAn morphological alterations, indicating autophagic compromise in DAn from ID-PD- and LRRK2-PD-iPSC, which we demonstrate occurs at the level of autophagosome clearance. Our study provides an iPSC-based in vitro model that captures the patients' genetic complexity and allows investigation of the pathogenesis of both sporadic and familial PD cases in a disease-relevant cell type.
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It is part of: EMBO Molecular Medicine, 2012, vol. 4, num. 5, p. 380-395
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ISSN: 1757-4676
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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